INFLAMATION AND CANCER

Transcription

1 INFLAMATION AND CANCER NANIALEI GOLDEN, M.D., F.A.C.R.O. RADIATION ONCOLOGY MEDICAL DIRECTOR, HEALTH FIRST CANCER SERVICES ASSISTANT PROFESSOR, UNIVERSITY OF CENTRAL FLORIDA COLLEGE OF MEDICINE

2 PROTO-ONCOGENE A normal gene that mutates and can give rise to cancer. Thousands of proto-oncogenes

3 INFLAMATION The Good, The Bad, and the Ugly Inflamation is the immune system s response to various insults The Good Protective The Bad Overstimulation is pathologic The Ugly If excessive, major scar tissue

4 THE GOOD Inflamation is the immune system s response to various insults Protective Pain limits further damage Clear bacteria and other pathogens

5 THE GOOD After cancer surgery, immune cells converge to stimulate healing High numbers of Tumor Infiltrating Lymphocytes (TIL s) conveys a protective effect with better outcomes CD3 + IM, CD8 + CCN

6 THE BAD Inflamation can lead to overstimulation of the immune system and lead to other diseases Inflamation associated with: Cancer Obesity Heart disease Stroke Autoimmune disorders (Lupus, Celiac Dz)

7 THE BAD Excessive inflamatory conditions: Asthma Chronic bladder infections Squamous Cell Carcinoma Inflamatory Bowel Diseases Ulcerative Colitis Crohn s Disease

8 THE UGLY Excessive inflamation leads to scar tissue. But it s not scar tissue you can see from the outside.

9 SMOKING STATISTICS 20% OF AMERICANS ARE SMOKERS # 1 RISK FACTOR FOR CANCER >1/3 OF 500,000 US CANCER DEATHS # 2 RISK FACTORS OBESITY, PHYSICAL INACTIVITY 1/3 OF 500,000 US CANCER DEATHS THUS ~2/3 OF CANCER DEATHS ARE POTENTIALLY PREVENTABLE

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13 PROTO-ONCOGENE Lung cancer and COPD (emphysema) are related. Both strongly associated with tobacco. COPD doubles the risk of lung cancer. c-src is mutated with cigarette smoke Inflamatory chemicals create a chain reaction MMP-9, -12, cathepsin G, K, IL-17, TNF-α, MCP-1 and KC Creates environment conducive to cancer.

14 WE VE COME A LONG WAY, BABY!!

15 FLORIDA OBESITY STATISTICS ADOLESCENTS BMI 15% OVERWEIGHT 11% OBESE ADULTS BMI 38% OVERWEIGHT 24% OBESE

16 BODY MASS INDEX OVERWEIGHT BMI OBESE BMI EXT OBESE BMI >40

17 ADOLESCENT OBESITY

18 ADULT OBESITY TRENDS

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21 OBESITY AND CANCER Inflamation can lead to overstimulation of the immune system and lead to other diseases Clear association Breast Colon Endometrium Esophagus Kidney

22 OBESITY AND CANCER RISK OF CANCER INCREASED FOR PANCREAS GALLBLADDER THYROID OVARIAN CERVIX MULTIPLE MYELOMA HODGKIN S LYMPHOMA AGGRESSIVE PROSTATE CANCER

23 OBESITY AND CANCER Surgery for morbid obesity Reduced mortality from diabetes, heart disease and cancer. Obesity is considered a low grade inflamatory disease

24 DIABETES Glucose rises, insulin rises to surpress Chronically elevated glucose overwhelms and insulin can t keep up Leads to Metabolic Syndrome Increase risk for heart disease Increases risk for cancer through growth factor stimulation

25 METABOLIC SYNDROME Risk factors that increase risk of heart disease, stroke and cancer Having 3 of 5 diagnostic for Met. Syndrome Large waistline (apple shape) High Triglycerides (or being on meds for it) Low HDL (the good cholesterol) High Blood Pressure (or being on meds for it) High fasting blood sugar

26 APPLE SHAPE Fatty deposition in the abdomen is a greater risk for heart disease than on the hips (pear shape). Chemicals released by abdominal fat are different than those in other parts of the body.

27 HIGH TRIGLYCERIDES Fat that is circulating in the blood stream Patients think that because they are on medication that their risk is back to baseline but that is false.

28 LOW HDL HDL helps remove cholesterol from the arteries. You can have totally normal LDL, cholesterol, and triglyceride levels but a low HDL increases risk of heart disease.

29 HIGH BLOOD PRESSURE Elevated pressure in the arteries causes damage. The damage incites an inflamatory response. That is what leads to the plaque build-up that clogs arteries Clogged carotid arteries increases risk of stroke Clogged heart arteries causes heart attacks

30 HIGH FASTING BLOOD SUGAR Mildly high glucose may be an early sign of diabetes.

31 METABOLIC SYNDROME One study estimated that 25% of US population has it. You don t have complete control. Genetics plays a role. Triglycerides, low HDL are familial BUT for most overweight/obese adults, weight reduction and a healthy lifestyle will lower BP and glucose, many can stop meds and reduce risk.

32 ROLE OF PLATELETS Platelets are what allows our blood to clot They have a direct relationship with inflamation through interaction with immune cells and endothelial cells. Damage to the lining of arteries causes platelets to recruit other cells that eventually leads to atherosclerosis.

33 MODIFIERS Aspirin and Cyclooxygenase(COX)-2 inhibitors (like Celebrex) Blocks certain inflamatory pathways Protective against heart disease ASA has some protection for colon cancer Side effects Bleeding, stomach ulcers

34 BACTERIA Infection stimulates an immune response Bacterial endocarditis linked to oral health Gut microbes linked to certain GI cancers

35 HEALTHY LIVING There is no food, pill, herb, liquid, or other concoction that is currently known to selectively attract the good immune cells and block the bad. Be skeptical of products that work with your immune system or boost your immune system

36 LIFESTYLE RECOMMENDATIONS POSTMENOPAUSAL WOMEN CALCIUM 1,200-1,500 mg/d VITAMIN D 800U/d WEIGHT-BEARING EXERCISE MODERATE ALCOHOL USE >1 DRINK / DAY SMOKING CESSATION

37 HEALTHY LIFESTYLE EAT LOTS OF FRUITS, VEGGIES, & WHOLE GRAINS EXERCISE REGULARLY MAINTAIN HEALTHY WEIGHT USE SUNSCREEN AVOID TANNING SALONS AVOID TOBACCO PRODUCTS WEAR YOUR SEATBELT ALCOHOL AND DRIVING DON T MIX AND NEITHER DO CELL PHONES

38 Dr. Nani Golden